DNA methylation derived systemic inflammation indices are associated with head and neck cancer development and survival

Srikant Ambatipudi; Ryan Langdon; Rebecca C. Richmond; Matthew Suderman; Devin C. Koestler; Karl T. Kelsey; Nabila Kazmi; Christopher Penfold; Karen M. Ho; Wendy McArdle; Susan M. Ring; Miranda Pring; Tim Waterboer; Michael Pawlita; Tom R. Gaunt; George Davey Smith; Steve Thomas; Andy R. Ness; Caroline L. Relton

doi:10.1016/j.oraloncology.2018.08.021

DNA methylation derived systemic inflammation indices are associated with head and neck cancer development and survival

Srikant Ambatipudi^*, Ryan Langdon, Rebecca C. Richmond, Matthew Suderman, Devin C. Koestler, Karl T. Kelsey, Nabila Kazmi, Christopher Penfold, Karen M. Ho, Wendy McArdle, Susan M. Ring, Miranda Pring, Tim Waterboer, Michael Pawlita, Tom R. Gaunt, George Davey Smith, Steve Thomas, Andy R. Ness, Caroline L. Relton

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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Abstract

Objectives: Head and neck squamous cell carcinoma (HNSCC) is often associated with chronic systemic inflammation (SI). In the present study, we assessed if DNA methylation-derived SI (mdSI) indices: Neutrophil-to-Lymphocyte ratio (mdNLR) and Lymphocyte-to-Monocyte ratio (mdLMR) are associated with the presence of HNSCC and overall survival (OS).

Materials and Methods: We used two peripheral blood DNA methylation datasets: an HNSCC case-control dataset (n= 183) and an HNSCC survival dataset (n= 407) to estimate mdSI indices. We then performed multivariate regressions to test the association between mdSI indices, HNSCC development and OS.

Results: Multivariate logistic regression revealed that elevated mdNLR was associated with increased odds of being an HNSCC case (OR=3.25, 95%CI = 2.14-5.34, P = 4x10-7) while the converse was observed for mdLMR (OR=0.88, 95%CI = 0.81-0.90, P = 2x10-3). In the HNSCC survival dataset, HPV16-E6 seropositive HNSCC cases had an elevated mdLMR (P = 9 x 10-5) and a lower mdNLR (P = 0.003) compared to seronegative patients. Multivariate Cox regression in the HNSCC survival dataset revealed that lower mdLMR (HR= 1.96, 95%CI =1.30-2.95, P = 0.0013) but not lower mdNLR (HR= 0.68, 95%CI = 0.46-1.00, P = 0.0501) was associated with increased risk of death.

Conclusion: Our results indicate that mdSI estimated by DNA methylation data is associated with the presence of HNSCC and overall survival. The mdSI indices may be used as a valuable research tool to reliably estimate SI in the absence of cell-based estimates. Rigorous validation of our findings in large prospective studies is warranted in the future.

Original language	English
Pages (from-to)	87-94
Number of pages	8
Journal	Oral Oncology
Volume	85
Early online date	5 Sept 2018
DOIs	https://doi.org/10.1016/j.oraloncology.2018.08.021
Publication status	Published - 1 Oct 2018

Research Groups and Themes

ICEP

Keywords

DNA methylation
Head and neck cancer
Lymphocyte-to-monocyte ratio
mdNLR
Neutrophil-to-lymphocyte ratio
Overall survival
Systemic inflammation

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Ambatipudi, S., Langdon, R., Richmond, R. C., Suderman, M., Koestler, D. C., Kelsey, K. T., Kazmi, N., Penfold, C., Ho, K. M., McArdle, W., Ring, S. M., Pring, M., Waterboer, T., Pawlita, M., Gaunt, T. R., Davey Smith, G., Thomas, S., Ness, A. R., & Relton, C. L. (2018). DNA methylation derived systemic inflammation indices are associated with head and neck cancer development and survival. Oral Oncology, 85, 87-94. https://doi.org/10.1016/j.oraloncology.2018.08.021

@article{af8f772c112f4ac38c313b15ce147cc9,

title = "DNA methylation derived systemic inflammation indices are associated with head and neck cancer development and survival",

abstract = "Objectives: Head and neck squamous cell carcinoma (HNSCC) is often associated with chronic systemic inflammation (SI). In the present study, we assessed if DNA methylation-derived SI (mdSI) indices: Neutrophil-to-Lymphocyte ratio (mdNLR) and Lymphocyte-to-Monocyte ratio (mdLMR) are associated with the presence of HNSCC and overall survival (OS). Materials and Methods: We used two peripheral blood DNA methylation datasets: an HNSCC case-control dataset (n= 183) and an HNSCC survival dataset (n= 407) to estimate mdSI indices. We then performed multivariate regressions to test the association between mdSI indices, HNSCC development and OS.Results: Multivariate logistic regression revealed that elevated mdNLR was associated with increased odds of being an HNSCC case (OR=3.25, 95%CI = 2.14-5.34, P = 4x10-7) while the converse was observed for mdLMR (OR=0.88, 95%CI = 0.81-0.90, P = 2x10-3). In the HNSCC survival dataset, HPV16-E6 seropositive HNSCC cases had an elevated mdLMR (P = 9 x 10-5) and a lower mdNLR (P = 0.003) compared to seronegative patients. Multivariate Cox regression in the HNSCC survival dataset revealed that lower mdLMR (HR= 1.96, 95%CI =1.30-2.95, P = 0.0013) but not lower mdNLR (HR= 0.68, 95%CI = 0.46-1.00, P = 0.0501) was associated with increased risk of death.Conclusion: Our results indicate that mdSI estimated by DNA methylation data is associated with the presence of HNSCC and overall survival. The mdSI indices may be used as a valuable research tool to reliably estimate SI in the absence of cell-based estimates. Rigorous validation of our findings in large prospective studies is warranted in the future.",

keywords = "DNA methylation, Head and neck cancer, Lymphocyte-to-monocyte ratio, mdNLR, Neutrophil-to-lymphocyte ratio, Overall survival, Systemic inflammation",

author = "Srikant Ambatipudi and Ryan Langdon and Richmond, {Rebecca C.} and Matthew Suderman and Koestler, {Devin C.} and Kelsey, {Karl T.} and Nabila Kazmi and Christopher Penfold and Ho, {Karen M.} and Wendy McArdle and Ring, {Susan M.} and Miranda Pring and Tim Waterboer and Michael Pawlita and Gaunt, {Tom R.} and {Davey Smith}, George and Steve Thomas and Ness, {Andy R.} and Relton, {Caroline L.}",

year = "2018",

month = oct,

day = "1",

doi = "10.1016/j.oraloncology.2018.08.021",

language = "English",

volume = "85",

pages = "87--94",

journal = "Oral Oncology",

issn = "1368-8375",

publisher = "Pergamon Press",

}

Ambatipudi, S, Langdon, R , Richmond, RC , Suderman, M, Koestler, DC, Kelsey, KT, Kazmi, N, Penfold, C, Ho, KM, McArdle, W, Ring, SM , Pring, M, Waterboer, T, Pawlita, M, Gaunt, TR , Davey Smith, G , Thomas, S, Ness, AR & Relton, CL 2018, 'DNA methylation derived systemic inflammation indices are associated with head and neck cancer development and survival', Oral Oncology, vol. 85, pp. 87-94. https://doi.org/10.1016/j.oraloncology.2018.08.021

TY - JOUR

T1 - DNA methylation derived systemic inflammation indices are associated with head and neck cancer development and survival

AU - Ambatipudi, Srikant

AU - Langdon, Ryan

AU - Richmond, Rebecca C.

AU - Suderman, Matthew

AU - Koestler, Devin C.

AU - Kelsey, Karl T.

AU - Kazmi, Nabila

AU - Penfold, Christopher

AU - Ho, Karen M.

AU - McArdle, Wendy

AU - Ring, Susan M.

AU - Pring, Miranda

AU - Waterboer, Tim

AU - Pawlita, Michael

AU - Gaunt, Tom R.

AU - Davey Smith, George

AU - Thomas, Steve

AU - Ness, Andy R.

AU - Relton, Caroline L.

PY - 2018/10/1

Y1 - 2018/10/1

N2 - Objectives: Head and neck squamous cell carcinoma (HNSCC) is often associated with chronic systemic inflammation (SI). In the present study, we assessed if DNA methylation-derived SI (mdSI) indices: Neutrophil-to-Lymphocyte ratio (mdNLR) and Lymphocyte-to-Monocyte ratio (mdLMR) are associated with the presence of HNSCC and overall survival (OS). Materials and Methods: We used two peripheral blood DNA methylation datasets: an HNSCC case-control dataset (n= 183) and an HNSCC survival dataset (n= 407) to estimate mdSI indices. We then performed multivariate regressions to test the association between mdSI indices, HNSCC development and OS.Results: Multivariate logistic regression revealed that elevated mdNLR was associated with increased odds of being an HNSCC case (OR=3.25, 95%CI = 2.14-5.34, P = 4x10-7) while the converse was observed for mdLMR (OR=0.88, 95%CI = 0.81-0.90, P = 2x10-3). In the HNSCC survival dataset, HPV16-E6 seropositive HNSCC cases had an elevated mdLMR (P = 9 x 10-5) and a lower mdNLR (P = 0.003) compared to seronegative patients. Multivariate Cox regression in the HNSCC survival dataset revealed that lower mdLMR (HR= 1.96, 95%CI =1.30-2.95, P = 0.0013) but not lower mdNLR (HR= 0.68, 95%CI = 0.46-1.00, P = 0.0501) was associated with increased risk of death.Conclusion: Our results indicate that mdSI estimated by DNA methylation data is associated with the presence of HNSCC and overall survival. The mdSI indices may be used as a valuable research tool to reliably estimate SI in the absence of cell-based estimates. Rigorous validation of our findings in large prospective studies is warranted in the future.

AB - Objectives: Head and neck squamous cell carcinoma (HNSCC) is often associated with chronic systemic inflammation (SI). In the present study, we assessed if DNA methylation-derived SI (mdSI) indices: Neutrophil-to-Lymphocyte ratio (mdNLR) and Lymphocyte-to-Monocyte ratio (mdLMR) are associated with the presence of HNSCC and overall survival (OS). Materials and Methods: We used two peripheral blood DNA methylation datasets: an HNSCC case-control dataset (n= 183) and an HNSCC survival dataset (n= 407) to estimate mdSI indices. We then performed multivariate regressions to test the association between mdSI indices, HNSCC development and OS.Results: Multivariate logistic regression revealed that elevated mdNLR was associated with increased odds of being an HNSCC case (OR=3.25, 95%CI = 2.14-5.34, P = 4x10-7) while the converse was observed for mdLMR (OR=0.88, 95%CI = 0.81-0.90, P = 2x10-3). In the HNSCC survival dataset, HPV16-E6 seropositive HNSCC cases had an elevated mdLMR (P = 9 x 10-5) and a lower mdNLR (P = 0.003) compared to seronegative patients. Multivariate Cox regression in the HNSCC survival dataset revealed that lower mdLMR (HR= 1.96, 95%CI =1.30-2.95, P = 0.0013) but not lower mdNLR (HR= 0.68, 95%CI = 0.46-1.00, P = 0.0501) was associated with increased risk of death.Conclusion: Our results indicate that mdSI estimated by DNA methylation data is associated with the presence of HNSCC and overall survival. The mdSI indices may be used as a valuable research tool to reliably estimate SI in the absence of cell-based estimates. Rigorous validation of our findings in large prospective studies is warranted in the future.

KW - DNA methylation

KW - Head and neck cancer

KW - Lymphocyte-to-monocyte ratio

KW - mdNLR

KW - Neutrophil-to-lymphocyte ratio

KW - Overall survival

KW - Systemic inflammation

UR - http://www.scopus.com/inward/record.url?scp=85052903895&partnerID=8YFLogxK

U2 - 10.1016/j.oraloncology.2018.08.021

DO - 10.1016/j.oraloncology.2018.08.021

M3 - Article (Academic Journal)

C2 - 30220325

AN - SCOPUS:85052903895

SN - 1368-8375

VL - 85

SP - 87

EP - 94

JO - Oral Oncology

JF - Oral Oncology

ER -

DNA methylation derived systemic inflammation indices are associated with head and neck cancer development and survival

Abstract

Research Groups and Themes

Keywords

UN SDGs

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Handle.net

Other files and links

Embargoed Document

Fingerprint

IEU 2 Relton Programme - Epigenetic Epidemiology

IEU: MRC Integrative Epidemiology Unit Quinquennial renewal

NIHR BRC Nutrition

Illumina Array

Professor George Davey Smith

Professor Tom R Gaunt

Dr Miranda Pring

Cite this

DNA methylation derived systemic inflammation indices are associated with head and neck cancer development and survival

Abstract

Research Groups and Themes

Keywords

UN SDGs

Access to Document

Handle.net

Other files and links

Embargoed Document

Fingerprint

Projects

IEU 2 Relton Programme - Epigenetic Epidemiology

IEU: MRC Integrative Epidemiology Unit Quinquennial renewal

NIHR BRC Nutrition

Equipment

Illumina Array

Profiles

Professor George Davey Smith

Professor Tom R Gaunt

Dr Miranda Pring

Cite this